What is a suitable substitute for Trelegy Ellipta (fluticasone furoate, umeclidinium, and vilanterol) in a patient with chronic obstructive pulmonary disease (COPD)?

Suitable Substitutes for Trelegy Ellipta in COPD

For patients requiring triple therapy, alternative single-inhaler triple combinations include budesonide/glycopyrronium/formoterol or beclometasone/glycopyrronium/formoterol, while patients with lower symptom burden or exacerbation risk should be stepped down to LAMA/LABA dual therapy without an inhaled corticosteroid. 1, 2

Decision Algorithm for Trelegy Substitution

Step 1: Assess Current Disease Severity and Exacerbation Risk

High-risk patients requiring continued triple therapy:

• ≥2 moderate exacerbations OR ≥1 hospitalization/ED visit in the past year 1
• FEV₁ <50% predicted with chronic bronchitis phenotype 1
• CAT score ≥10 or mMRC ≥2 with FEV₁ <80% predicted 1
• Blood eosinophil count ≥150 cells/mm³ (predicts better ICS response) 3
• Features of asthma-COPD overlap syndrome 3, 2

For these patients, substitute with alternative triple therapy combinations:

• Budesonide/formoterol/glycopyrronium (single inhaler) 2
• Beclometasone/formoterol/glycopyrronium (single inhaler) 2

Step 2: Consider De-escalation for Lower-Risk Patients

Patients who may not require triple therapy should be stepped down to LAMA/LABA dual therapy:

• ≤1 moderate exacerbation in the past year without hospitalization 1
• Moderate symptoms (CAT ≥10, mMRC ≥2) with FEV₁ <80% predicted but stable disease 1
• Concerns about pneumonia risk (ICS increases pneumonia risk with number needed to harm of 33 patients per year) 4

LAMA/LABA dual therapy is preferred over ICS/LABA because:

• Superior lung function improvements compared to ICS/LABA 1
• Lower rates of adverse events, particularly pneumonia 1
• LAMA/LABA was superior to LABA/ICS in preventing exacerbations in Group D patients 1

Step 3: Initiate Appropriate Monotherapy for Mild Disease

For patients with low symptom burden (CAT <10) and FEV₁ ≥80% predicted:

• Start with single long-acting bronchodilator (LAMA or LABA) 1
• LAMA is preferred over LABA for exacerbation prevention 1
• Short-acting bronchodilators as needed for all patients across the spectrum 1

Alternative Triple Therapy Options

Single-inhaler triple combinations available as Trelegy substitutes:

• These contain ICS/LAMA/LABA in various formulations 2
• Single-inhaler triple therapy (SITT) is preferred over multiple inhalers for improved adherence 1
• Once-daily administration improves treatment adherence and efficacy 5

Critical Pitfalls to Avoid

Never add a separate ICS (like Pulmicort) to Trelegy:

• This exposes patients to duplicate ICS therapy without guideline support 4
• Increases pneumonia risk without additional benefit 4
• When transitioning from ICS/LABA to triple therapy, discontinue the previous ICS-containing regimen 4

Do not use ICS monotherapy:

• ICS monotherapy is not recommended for stable COPD patients with low exacerbation risk 1
• Always combine ICS with at least one long-acting bronchodilator 1

Avoid beta-blockers (including eye drops):

• These should be avoided in all COPD patients as they antagonize bronchodilator effects 1

Additional Therapies for Persistent Exacerbations

If patients continue to exacerbate on triple therapy:

• Add roflumilast for patients with FEV₁ <50% predicted and chronic bronchitis, particularly if hospitalized for exacerbation in the previous year 1
• Consider prophylactic macrolide in former smokers (weigh risk of resistant organisms) 1
• Evaluate for pulmonary rehabilitation rather than medication escalation 4

Cardiovascular Considerations

When selecting LABA-containing medications:

• Consider cardiovascular comorbidities as LABAs may have cardiac effects 3
• Monitor for cardiovascular adverse events, though triple therapy studies show acceptable safety profiles 5